AZD0754 for Prostate Cancer

(APOLLO Trial)

Recruiting at 8 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 0

Duration: Variable, up to 2 years

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and antitumour activity of AZD0754 CAR T-cell therapy in participants with metastatic prostate cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must continue any medical castration therapy if you are on it, and you cannot receive certain full-dose anticoagulants or recent anticancer therapies close to the study start. It's best to discuss your specific medications with the study team.

What safety data exists for AZD0754 in humans?

There is no specific safety data available for AZD0754, but a similar compound, AZD3514, has been evaluated in clinical trials for prostate cancer, showing it is generally safe in humans. ^{1 2 3 4 5}

How does the drug AZD0754 differ from other prostate cancer treatments?

AZD0754 is unique because it likely targets androgen receptor (AR) signaling, similar to AZD3514, which inhibits both androgen-dependent and independent AR signaling. This approach is particularly important for treating castration-resistant prostate cancer, where traditional hormone therapies fail. ^{1 3 6 7 8}

Eligibility Criteria

This trial is for individuals with metastatic prostate cancer. Participants should meet specific health criteria to be eligible, but the exact inclusion and exclusion details are not provided.

Inclusion Criteria

My prostate cancer is growing despite hormone therapy.

My prostate cancer has spread, and it's not small cell or neuroendocrine type.

I have had treatments like abiraterone or taxane for prostate cancer, or I cannot or will not take taxane.

Exclusion Criteria

Participants with prior solid organ transplantation

I had cancer before, but it was treated over 2 years ago and is not likely to come back.

I have brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD0754 CAR T-cell therapy to evaluate safety, tolerability, and antitumour activity

Variable, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• AZD0754

Trial Overview The study is testing AZD0754 CAR T-cell therapy's safety, how well people can handle it, and its effectiveness in treating metastatic prostate cancer.

Participant Groups

Group I: AZD0754 Experimental Treatment 1 Intervention

AZD0754 monotherapy for treatment of participants with metastatic prostate cancer.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

AZD3514 is an orally bioavailable drug that effectively inhibits both androgen-dependent and -independent signaling of the androgen receptor (AR), which is crucial for treating castration-resistant prostate cancer (CRPC).

The drug works through two mechanisms: it prevents the nuclear translocation of the AR and reduces the overall levels of the receptor, demonstrating significant antitumor activity in animal models, including juvenile male rats and the HID28 mouse model of CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Loddick, SA., Ross, SJ., Thomason, AG., et al.[2021]

In a 7-year study involving patients with early, non-metastatic prostate cancer, adding bicalutamide (150 mg) to standard care significantly improved progression-free survival (PFS) for those with locally advanced disease, reducing the risk of progression by 34%.

However, in cases of localized disease, bicalutamide did not show a significant benefit in PFS, and there was no difference in overall survival between the treatment and standard care groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. Wirth, M., Tyrrell, C., Delaere, K., et al.[2014]

The study developed and validated an immunohistochemistry (IHC) method to assess androgen receptor (AR) levels in circulating tumor cells (CTCs) for patients undergoing treatment with AZD3514, a drug targeting prostate cancer.

Initial reproducibility tests showed almost perfect agreement between operators in scoring AR positivity (κ=0.94), but a bias in staining intensity was corrected through additional training, improving agreement to κ=0.81, demonstrating the method's reliability and potential for broader application in IHC techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells. Cummings, J., Sloane, R., Morris, K., et al.[2021]

In a study involving 60 hormone-naïve prostate cancer patients, the combination of combined androgen blockade (CAB) with zoledronic acid (ZA) significantly reduced the incidence of skeletal-related events (SREs) and bone pain compared to CAB alone.

Patients with a Gleason score of 8 or higher showed improved progression-free survival (PFS) when treated with CAB-ZA, suggesting that this combination therapy is particularly beneficial for those with more aggressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of combined androgen blockade with zoledronic acid treatment in prostate cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade trial on prostate cancer) study. Ueno, S., Mizokami, A., Fukagai, T., et al.[2022]

In a study of 105 prostate cancer patients with bone metastases, combining zoledronic acid (ZA) with docetaxel-based chemotherapy improved bone progression-free survival (9.0 months vs. 6.0 months) and overall survival (19.0 months vs. 15.0 months) compared to chemotherapy alone.

While the combination treatment did not show a significant difference in prostate-specific antigen (PSA) response rates, it was found to be safe, with no notable differences in adverse events between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel with or without zoledronic acid for castration-resistant prostate cancer. Pan, Y., Jin, H., Chen, W., et al.[2021]

In a study of 441 prostate tissue samples, MRP4 expression was found to be widely present in both benign and cancerous tissues, but it decreased as tumors progressed towards castrate-resistant disease.

Lower levels of MRP4 were linked to shorter PSA relapse-free survival times in androgen-dependent prostate cancer, suggesting that MRP4 expression could serve as a prognostic marker for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression. Montani, M., Hermanns, T., Müntener, M., et al.[2021]

ZIC5 is upregulated in prostate cancer, especially in metastatic cases, and its inhibition reduces cancer cell invasion and metastasis, indicating its role in promoting aggressive cancer behavior.

The study reveals that ZIC5 and the androgen receptor (AR) enhance each other's expression, contributing to metastasis and resistance to enzalutamide treatment, suggesting that targeting both ZIC5 and AR could be a promising strategy for treating advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AR-regulated ZIC5 contributes to the aggressiveness of prostate cancer. Tan, YF., Zhang, Y., Ge, SY., et al.[2022]

In a study of 302 men who underwent radical prostatectomy for localized prostate cancer, low expression of the biomarker zinc-alpha 2-glycoprotein (AZGP1) was linked to a significantly higher risk of biochemical failure, castration-based treatment, and developing castration-resistant prostate cancer over a median follow-up of 14 years.

The analysis showed that men with low AZGP1 expression had more than double the risk of aggressive outcomes compared to those with high expression, indicating that AZGP1 could be a valuable predictor for treatment decisions in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis. Kristensen, G., Berg, KD., Toft, BG., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of combined androgen blockade with zoledronic acid treatment in prostate cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade trial on prostate cancer) study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Docetaxel with or without zoledronic acid for castration-resistant prostate cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

AR-regulated ZIC5 contributes to the aggressiveness of prostate cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis. [2020]